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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this work was to study the effect of diabetes on 125I-labelled insulin-like growth factor (IGF) binding to specific serum binding proteins (IGFBPs) and the possible role of protein glycation in such an effect. Accordingly, ligand blotting and fructosamine assays were performed in serum samples from diabetic and non-diabetic eSS rats as well as in samples of normal rat serum previously incubated with different concentrations of glucose. IGFBPs with molecular weights of 24, 30 and 40 kDa were identified in samples from diabetic and non-diabetic rats. 125I-Labelled IGF-I binding to each of these fractions increased significantly in the serum of diabetic rats. IGF-I binding to IGFBP-40 increased significantly as a function of the degree of glycation of serum proteins. Conversely, the increased binding of IGFBP-24 and IGFBP-30 was related only to the glucose concentration attained at 120 min during the oral glucose tolerance test. Glycation of proteins of normal serum and the binding of labelled IGF-I increased as a function of glucose concentration in the incubation media. In these in-vitro glycated normal sera, only the binding to IGFBP-40 increased significantly; this increase was closely related to the amount of protein glycation. No clear and reproducible changes occurred with the binding of 125I-labelled IGF-I to IGFBP-24 and IGFBP-30 fractions. These results confirm the increase in the binding capacity of IGFBPs reported in diabetic animals. They also show that the increase in IGF-I binding to each IGFBP fraction is regulated by a different mechanism; whereas protein glycation induces changes in IGFBP-40, this mechanism does not affect the binding properties of the other two IGFBPs. The increased binding of IGFBP might affect the availability of free IGF-I, and the consequent alterations in IGF-I-dependent metabolic processes could explain the role of this growth factor in the pathogenesis of chronic complications of diabetes.
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PMID:Protein glycation: its role in the changes induced by diabetes in the properties of the serum insulin-like growth factor-I binding proteins. 172 Aug 5

Testicular blood vessels contain IGF-I and IGF-II/M6P receptors. Binding to these receptors was altered following treatment with streptozotocin to induce diabetes. Intensity of labelling and size of receptors were examined using SDS-gel electrophoresis and autoradiography. The IGF-I and IGF-II/M6P receptor of the diabetic rat testicular microvessels appear to have a lower molecular weight as compared to controls. Macro- and microvascular tissues from diabetic rats apparently contain more IGF-I receptors than normal Sprague-Dawley rats. Using immunohistochemical techniques, the IGF-II/M6P receptor appears to dissociate easier from diabetic rat testicular arteries than from control animal blood vessels. M6P appears to increase both IGF-I and IGF-II binding to the rat IGF-II/M6P receptor, at least as visualized using affinity crosslinking analysis. Whether these differences in the IGF receptors are involved in the development of diabetic vascular disease is not yet known.
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PMID:Insulin-like growth factor receptors in testicular vascular tissue from normal and diabetic rats. 172 19

Results obtained from our analyses of the role of hormones and growth factors in rat embryonic and fetal development are reviewed. Whole 10-day embryos or structures from 14-16-day fetuses (paws, intestines, reproductive tracts) were transplanted under the kidney capsule of syngeneic host rats of different age, sex, physiological state or level of nutrition. In intact hosts, fetal transplants grew almost as much as they would have if left in situ in the fetuses, and tissue differentiation in them was essentially normal. By contrast, growth of embryo transplants was severely depressed relative to their growth in utero, but tissue differentiation was only slightly retarded. Fetal paws grew equally well in female hosts widely diverging in age and growth rate. Thus, in such hosts growth of the fetal paw was highly independent of the growth rate of the hosts. In hosts in which growth was arrested or reduced by diabetes, hypophysectomy or food restriction, growth of paw transplants was impaired, but not as severely as that of the hosts themselves. Fetal skeletal structures were relatively independent of thyroid hormones (TH) for growth; TH dependence developed progressively postnatally. In pregnant hosts, fetal paw transplants grew as well during the first half of gestation as they did in virgin females. By contrast, during the second half of pregnancy and during both halves of the lactational period, growth of the transplants was significantly reduced. Host skeletal growth was also inhibited during late pregnancy and throughout lactation. The impaired growth during the second half of gestation was associated with a large reduction in serum IGF-I concentration and a resistance to the growth-promoting actions of GH. In the lactating hosts, serum IGF-I concentration returned almost to prepregnancy levels and the resistance to GH persisted, but at a reduced level. The direct effects of hormones, growth factors, and antibodies to them on growth and tissue differentiation in the transplants were assessed using infusion methods. Substances were infused into the renal artery of transplant-bearing kidneys via catheters attached to osmotic minipumps. The direct effects of insulin, GH, IGFs, basic FGF and EGF on transplant growth and tissue differentiation were evaluated. Insulin directly stimulated growth of transplants in diabetic hosts but GH did not have a direct effect in hypophysectomized rats. The growth-restorative effects of GH observed in hypophysectomized hosts were apparently mediated indirectly via IGF-I. Infused rat IGF-II (MSA) was more effective at stimulating growth of embryo transplants than was recombinant human IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Analysis of the role of hormones and growth factors in growth control and tissue differentiation using transplanted mammalian embryos and fetal structures. 184 45

The measurement of serum insulin-like growth factors (IGFs) in serum is complicated by the presence of high affinity IGF-binding proteins. The accurate measurement of IGFs by radioligand binding assays requires that the interference from binding proteins be eliminated. Acid-gel chromatography, the standard method for removing binding proteins, is laborious and time consuming. Alternative methods for extracting serum IGFs include the use of HCl-ethanol treatment and reverse phase minicolumns. However, these methods are unsuitable for use with serum for some species, such as rat and sheep, due to incomplete removal of binding proteins. We developed a fast protein liquid chromatography size-exclusion chromatographic method for characterizing the presence of IGF-binding proteins in physiological fluids and used this method to systematically investigate different combinations of acids and organic solvents as potential extraction methods for IGFs. We developed and validated an improved extraction procedure that uses formic acid, Tween-20, and acetone. The new extraction method was used in conjunction with purified biosynthetic human IGF-II and a commercially available anti-IGF-II monoclonal antibody in the development of an improved RIA for IGF-II. The new RIA is sensitive (5.0 pg/tube), specific (IGF-I cross-reactivity, less than 1%), and reproducible [interassay precision (coefficient of variation), less than 9.2%). We measured the serum concentrations of IGF-II in adults and found a significant difference between normal subjects and individuals with insulin-dependent diabetes mellitus.
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PMID:Measurement of insulin-like growth factor-II in physiological fluids and tissues. I. An improved extraction procedure and radioimmunoassay for human and rat fluids. 198 63

The influence of metabolic control (HbA1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11-17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA1c values ranged from 8.2% to 12.9% (normal range 5.5-8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r = -0.66) and NA and ERPF (r = -0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA1c (r = 0.63, r = 0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.
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PMID:Factors related to renal haemodynamics in young type-1 diabetes mellitus patients. 208 57

Conflicting data are found in the literature concerning the growth hormone response to growth hormone-releasing hormone and the insulin-like growth factor I level in Type I diabetes mellitus. The GH response to GHRH and the serum IGF-I level were studied in 29 moderately to well regulated male diabetic patients and 20 age-matched controls. The mean fasting glucose and HbA1c (normal less than 6.5%) levels were, respectively: 10.2 +/- 0.8 mmol/l and 7.1 +/- 0.2%, and 4.1 +/- 0.1 mmol/l and 5.4 +/- 0.1% (mean +/- SEM). The GH response to GHRH was higher in the diabetic patients at 15, 30 and 45 min (p less than 0.05), and also delta peak GH was higher compared with controls: 34.8 +/- 5.6 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). The serum IGF-I level was lower in the diabetic patients: 460 +/- 30 vs 700 +/- 60 U/l (p less than 0.01). No correlations could be demonstrated between delta peak GH, serum IGF-I or HbA1c level. When only patients with a mean fasting glucose less than or equal to 7.0 mmol/l and normal HbA1c (5.8 +/- 0.3%) were analysed, delta peak GH was also elevated compared with controls: 47.0 +/- 16.3 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). No difference was observed in GH response or serum IGF-I level in 5 patients with (pre)proliferative retinopathy compared with patients without this complication. It is concluded that in Type I diabetes the GH response to GHRH is increased, even in well regulated patients, and that the serum IGF-I level is depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone in type I diabetic and healthy man. 211 Apr 12

We investigated the cellular mechanisms responsible for growth hormone (GH) resistance in diabetes and malnutrition in the rat. In insulin-dependent diabetes, a post-receptor defect participates in GH resistance. During fasting, there is a loss of liver GH binding sites. Dietary protein restriction causes a post-receptor defect. This defect can be attributed to the combined effects of decreased liver IGF-I mRNA content and impaired message translation.
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PMID:[Diabetes, malnutrition and growth retardation]. 211 33

We recently identified a 32 K mol wt insulin-like growth factor (IGF)-binding protein (BP) which is markedly increased in the serum of streptozotocin-diabetic rats and recognized by antiserum against the human amniotic fluid IGFBP (hIGFBP-1). In the present study we sought to confirm that this protein represents the rat homolog of IGFBP-1 (rIGFBP-1), and that rIGFBP-1 may, therefore, play an important role in the regulation of IGF bioactivity in experimental diabetes. Since the abundance of related hepatic mRNA is high in diabetic rats, we asked whether well differentiated H4EIIC3 rat hepatoma cells produce rIGFBP-1 and provide sufficient amounts of this protein for purification and further characterization. Specific IGF-binding activity in hepatoma conditioned medium was detected initially by incubation with 125I-labeled recombinant human IGF-II and precipitation with polyethylene glycol. Ligand blotting demonstrated a 32 K BP, identical in size to the major low mol wt IGFBP found in diabetic rat serum. Affinity labeling and immunoprecipitation confirmed that this BP is related to human IGFBP-1 and is distinct from the fetal rat IGFBP, rIGFBP-2. Incorporation of [35S]methionine into 32 K BPs confirmed synthesis by hepatoma cells. For purification of BPs, conditioned medium was collected in roller culture, and BPs were purified by ammonium sulfate precipitation, Sephadex G-75 chromatography, and reverse phase HPLC. Partial amino acid sequencing of purified protein demonstrated 68% identity with the human IGFBP-1 and distinguished this BP from previously characterized rat IGFBPs. Purified protein bound both IGF-I and IGF-II with high affinity. We conclude that the 32 K IGFBP produced by H4EIIC3 hepatoma cells in culture represents the rat form of IGFBP-1 (rIGFBP-1). Regulation of rIGFBP-1 may play an important role in the modulation of IGF bioactivity in experimental animals with metabolic disease. The availability of purified rIGFBP-1 and identification of a cell line that produces this BP will greatly facilitate future studies of IGFBP-1 in the rat model.
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PMID:Production of the rat type 1 insulin-like growth factor-binding protein by well differentiated H4EIIC3 hepatoma cells: identification, purification, and N-terminal amino acid analysis. 216 20

When insulin was administered to streptozotocin-induced diabetic female rats, the percentage of glycohemoglobin, growth rate, ovulatory cycle, uterus to body weight ratio, and insulin-like growth factor (IGF-I) level returned to near normal. In untreated diabetic rats there were no normal estrous cycles, and hepatic IGF-I mRNA (7.94 +/- 1.02 O.D. units per micrograms total RNA) levels were significantly lower than the control or insulin-treated groups in proestrus (16.47 +/- 0.91 and 17.15 +/- 1.84, respectively). Insulin therapy restored the hypothalamic-pituitary-ovarian axis with the reinstitution of normal estrous cycles. Plasma IGF-I levels were highest in non-diabetic proestrous animals (277 +/- 36.9 ng/ml), significantly higher than IGF-I levels in insulin-treated diabetic rats in diestrus (174 +/- 23.1 ng/ml), non-diabetic diestrus rats (165 +/- 18.4 ng/ml) and untreated diabetic rats (135 +/- 19.7 ng/ml). Plasma IGF-I levels were elevated in insulin-treated diabetic rats in proestrus (221 +/- 78.3 ng/ml), however this was not significantly different from any other group. The increases observed in plasma IGF-I and hepatic IGF-I mRNA after insulin therapy correlate with the normalization of sex hormone secretion. Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrus groups.
Diabetes Res Clin Pract 1990 Mar
PMID:The effect of ovarian function on insulin-like growth factor I plasma levels and hepatic IGF-I mRNA levels in diabetic rats treated with insulin. 218 62

At present the pathogenesis of diabetic nephropathy remains unresolved. Clearly lack of insulin, with its associated disorders of carbohydrate, protein, and/or lipid metabolism, initiates the process which eventually leads to the characteristic histologic picture of diabetic nephropathy. The disturbance in cellular metabolism per se could directly injure the kidney by altering the energy needs of the cell or by leading to the accumulation of cellular toxins (ie, polyols) or by causing the deficiency of key cellular metabolites (ie, myoinositol). Elevation of the plasma glucose concentration enhances the glycosylation of proteins, which in turn can lead to glomerular basement membrane thickening, loss of charge selectivity, and direct cellular damage. The multiple disturbances in intermediary metabolism are associated with increased levels of and/or enhanced sensitivity to a variety of growth factors, including IGF-I and angiotensin, and this could lead to glomerular hypertrophy. An increase in the filtered load and subsequent reabsorption of electrolytes and metabolites also could contribute to renal hypertrophy. In all animal models of nephropathy, including diabetes, glomerular hypertrophy has been shown to be the best correlate of glomerular sclerosis, proteinuria, and progressive renal deterioration. The potential mechanisms by which glomerular hypertrophy can lead to renal histologic damage were discussed previously. By increasing the luminal diameter, glomerular hypertrophy also would be expected to augment wall tension and thereby increase intraglomerular pressure. Derangements in cellular metabolism or altered sensitivity to angiotensin also can directly elevate the intraglomerular pressure and lead to structural renal damage. In this schema, elevated intraglomerular pressure is but one of many pathogenic factors that contribute to the development of diabetic glomerulopathy and albuminuria. The precise role of increased glomerular pressure in the evolution of diabetic nephropathy remains uncertain at present. In rats, severe diabetic nephropathy can occur without an increase in Pgc, while in humans, hyperfiltration does not appear to be a predictor of proteinuria and renal dysfunction. Lastly, it is likely that a variety of other factors, including the coagulation system, plasma/cell lipid levels, prostaglandins, etc, also play a role in the pathogenesis of diabetic nephropathy. According to the outline presented in Figure 1, it is unlikely that any single factor will be sufficient to explain the development of diabetic glomerulosclerosis. Ultimately, the origin of diabetic nephropathy in IDDM must be traced to insulin lack, with its associated derangements in cellular metabolism. Therefore, the importance of tight glucose control should not be underemphasized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hyperfiltration and diabetic nephropathy: is it the beginning? Or is it the end? 219 Feb 80


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